AGRESTIA ZEROVII (MEGASPORACEAE, LICHEN-FORMING ASCOMYCETES), A NEW SPECIES FROM SOUTH EASTERN EUROPE PROVED BY ALTERNATIVE PHYLOGENETIC ANALYSIS

Agrestia zerovii is described, illustrated, and compared here with closely related taxa. It is a member of the A. hispida complex of the steppe zone of Ukraine, southeastern Europe, and diff ers from A. hispida s. str. in having much thicker main thalline lobes, in forming thick “horizontal crust”, and in the lack of black tips of secondary branchlets. Th e position of the newly described A. zerovii in the alternative combined phylogenetic tree of the Megasporaceae with all members for which reliable data on the nrITS, nrLSU, and mtSSU sequences are hitherto available is discussed. Four new robust branches and their taxonomic diversity are discussed, i.e.: the Agrestia, the Chlorangium, the Sphaerothallia s. str., and the “Circinaria” lacunosa clades being in separate position from the Circinaria s. str. clade (additionally to fi ve genera of the Megasporaceae, i.e. Aspicilia, Circinaria, Lobothallia, Megaspora and Sagedia accepted by previous authors). Th e genera Agrestia, Chlorangium, and Sphaerothallia, proposed to be resurrected, and a number of aspicilioid lichens the status of which are in need of revision are discussed. Five new combinations for the species of the genus Chlorangium (C. alpicola, C. aschabadense, C. asperum, C. gyrosum, and C. sphaerothallinum) are proposed

50 Years of Test (Un)fairness: Lessons for Machine Learning

Quantitative definitions of what is unfair and what is fair have been introduced in multiple disciplines for well over 50 years, including in education, hiring, and machine learning. We trace how the notion of fairness has been defined within the testing communities of education and hiring over the past half century, exploring the cultural and social context in which different fairness definitions have emerged. In some cases, earlier definitions of fairness are similar or identical to definitions of fairness in current machine learning research, and foreshadow current formal work. In other cases, insights into what fairness means and how to measure it have largely gone overlooked. We compare past and current notions of fairness along several dimensions, including the fairness criteria, the focus of the criteria (e.g., a test, a model, or its use), the relationship of fairness to individuals, groups, and subgroups, and the mathematical method for measuring fairness (e.g., classification, regression). This work points the way towards future research and measurement of (un)fairness that builds from our modern understanding of fairness while incorporating insights from the past.Comment: FAT* '19: Conference on Fairness, Accountability, and Transparency (FAT* '19), January 29--31, 2019, Atlanta, GA, US

Sequencing strategies and characterization of 721 vervet monkey genomes for future genetic analyses of medically relevant traits

Background We report here the first genome-wide high-resolution polymorphism resource for non-human primate (NHP) association and linkage studies, constructed for the Caribbean-origin vervet monkey, or African green monkey (Chlorocebus aethiops sabaeus), one of the most widely used NHPs in biomedical research. We generated this resource by whole genome sequencing (WGS) of monkeys from the Vervet Research Colony (VRC), an NIH-supported research resource for which extensive phenotypic data are available. Results We identified genome-wide single nucleotide polymorphisms (SNPs) by WGS of 721 members of an extended pedigree from the VRC. From high-depth WGS data we identified more than 4 million polymorphic unequivocal segregating sites; by pruning these SNPs based on heterozygosity, quality control filters, and the degree of linkage disequilibrium (LD) between SNPs, we constructed genome-wide panels suitable for genetic association (about 500,000 SNPs) and linkage analysis (about 150,000 SNPs). To further enhance the utility of these resources for linkage analysis, we used a further pruned subset of the linkage panel to generate multipoint identity by descent matrices. Conclusions The genetic and phenotypic resources now available for the VRC and other Caribbean-origin vervets enable their use for genetic investigation of traits relevant to human diseases

Complementation of hypersensitivity to DNA interstrand crosslinking agents demonstrates that XRCC2 is a Fanconi anaemia gene

Background Fanconi anemia (FA) is a heterogeneous inherited disorder clinically characterized by progressive bone marrow failure, congenital anomalies, and a predisposition to malignancies. Objective Determine, based on correction of cellular phenotypes, whether XRCC2 is a FA gene. Methods Cells (900677) from a previously identified patient with biallelic mutation of XRCC2, among other mutations, were genetically complemented with wild-type XRCC2. Results Wild-type XRCC2 corrects each of three phenotypes characteristic of FA cells, all related to the repair of DNA interstrand crosslinks, including increased sensitivity to mitomycin C (MMC), chromosome breakage, and G2-M accumulation in the cell cycle. Further, the p.R215X mutant of XRCC2, which is harbored by the patient, is unstable. This provides an explanation for the pathogenesis of this mutant, as does the fact that 900677 cells have reduced levels of other proteins in the XRCC2-RAD51B-C-D complex. Also, FANCD2 monoubiquitination and foci formation, but not assembly of RAD51 foci, are normal in 900677 cells. Thus, XRCC2 acts late in the FA-BRCA pathway as also suggested by hypersensitivity of 900677 cells to ionizing radiation. These cells also share milder sensitivities toward olaparib and formaldehyde with certain other FA cells. Conclusions XRCC2/FANCU is a FA gene, as is another RAD51 paralog gene, RAD51C/FANCO. Notably, similar to a subset of FA genes that act downstream of FANCD2, biallelic mutation of XRCC2/FANCU has not been associated with bone marrow failure. Taken together, our results yield important insights into phenotypes related to FA and its genetic origins

TET3 plays a critical role in white adipose development and diet-induced remodeling

Maintaining healthy adipose tissue is crucial for metabolic health, requiring a deeper understanding of adipocyte development and response to high-calorie diets. This study highlights the importance of TET3 during white adipose tissue (WAT) development and expansion. Selective depletion of Tet3 in adipose precursor cells (APCs) reduces adipogenesis, protects against diet-induced adipose expansion, and enhances whole-body metabolism. Transcriptomic analysis of wild-type and Tet3 knockout (KO) APCs unveiled TET3 target genes, including Pparg and several genes linked to the extracellular matrix, pivotal for adipogenesis and remodeling. DNA methylation profiling and functional studies underscore the importance of DNA demethylation in gene regulation. Remarkably, targeted DNA demethylation at the Pparg promoter restored its transcription. In conclusion, TET3 significantly governs adipogenesis and diet-induced adipose expansion by regulating key target genes in APCs

In vitro interaction network of a synthetic gut bacterial community

A key challenge in microbiome research is to predict the functionality of microbial communities based on community membership and (meta)-genomic data. As central microbiota functions are determined by bacterial community networks, it is important to gain insight into the principles that govern bacteria-bacteria interactions. Here, we focused on the growth and metabolic interactions of the Oligo-Mouse-Microbiota (OMM12) synthetic bacterial community, which is increasingly used as a model system in gut microbiome research. Using a bottom-up approach, we uncovered the directionality of strain-strain interactions in mono- and pairwise co-culture experiments as well as in community batch culture. Metabolic network reconstruction in combination with metabolomics analysis of bacterial culture supernatants provided insights into the metabolic potential and activity of the individual community members. Thereby, we could show that the OMM12 interaction network is shaped by both exploitative and interference competition in vitro in nutrient-rich culture media and demonstrate how community structure can be shifted by changing the nutritional environment. In particular, Enterococcus faecalis KB1 was identified as an important driver of community composition by affecting the abundance of several other consortium members in vitro. As a result, this study gives fundamental insight into key drivers and mechanistic basis of the OMM12 interaction network in vitro, which serves as a knowledge base for future mechanistic in vivo studies

Effect of a physical activity intervention on lower body bone health in childhood cancer survivors: A randomized controlled trial (SURfit)

It remains controversial whether physical activity promotes bone health in childhood cancer survivors (CCS). We aimed to assess the effect of a one-year general exercise intervention on lower body bone parameters of CCS. CCS ≥16 years at enrollment, -1. A nonstandardized personalized exercise programs might not be specific enough to promote bone health in CCS, although those compliant and those most in need may benefit. Future trials should include bone stimulating exercise programs targeting risk groups with reduced bone health and motivational features to maximize compliance

Plasticity and dystonia: a hypothesis shrouded in variability.

Studying plasticity mechanisms with Professor John Rothwell was a shared highlight of our careers. In this article, we discuss non-invasive brain stimulation techniques which aim to induce and quantify plasticity, the mechanisms and nature of their inherent variability and use such observations to review the idea that excessive and abnormal plasticity is a pathophysiological substrate of dystonia. We have tried to define the tone of our review by a couple of Professor John Rothwell's many inspiring characteristics; his endless curiosity to refine knowledge and disease models by scientific exploration and his wise yet humble readiness to revise scientific doctrines when the evidence is supportive. We conclude that high variability of response to non-invasive brain stimulation plasticity protocols significantly clouds the interpretation of historical findings in dystonia research. There is an opportunity to wipe the slate clean of assumptions and armed with an informative literature in health, re-evaluate whether excessive plasticity has a causal role in the pathophysiology of dystonia

Non-linear evolution in CCFM: The interplay between coherence and saturation

We solve the CCFM equation numerically in the presence of a boundary condition which effectively incorporates the non-linear dynamics. We retain the full dependence of the unintegrated gluon distribution on the coherence scale, and extract the saturation momentum. The resulting saturation scale is a function of both rapidity and the coherence momentum. In Deep Inelastic Scattering this will lead to a dependence of the saturation scale on the photon virtuality in addition to the usual x-Bjorken dependence. At asymptotic energies the interplay between the perturbative non-linear physics, and that of the QCD coherence, leads to an interesting and novel dynamics where the saturation momentum itself eventually saturates. We also investigate various implementations of the "non-Sudakov" form factor. It is shown that the non-linear dynamics leads to almost identical results for different form factors. Finally, different choices of the scale of the running coupling are analyzed and implications for the phenomenology are discussed.Comment: 37 pages, 21 figure

Fitness Ranking of Individual Mutants Drives Patterns of Epistatic Interactions in HIV-1

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